Jian Liu

Publications (3)19.07 Total impact

• Article: Site-specific acetylation of the proteasome activator REGγ directs its heptameric structure and functions.

  Jiang Liu, Ying Wang, Lei Li, Li Zhou, Haibin Wei, Qingxia Zhou, Jian Liu, Weicang Wang, Lei Ji, Peipei Shan, Yan Wang, Yuanyuan Yang, Sung Yun Jung, Pei Zhang, Chuangui Wang, Weiwen Long, Bianhong Zhang, Xiaotao Li
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  ABSTRACT: The proteasome activator REGγ has been reported to promote degradation of Steroid receptor coactivator-3 (SRC-3) and cyclin-dependent kinase inhibitors p21, p16, and p19 in a ubiquitin and ATP independent manner. A recent comparative analysis of REGγ expression in mouse and human tissues reveals a unique pattern of REGγ in specific cell types, suggesting undisclosed functions and biological importance of this molecule. Despite the emerging progress made in REGγ-related studies, how REGγ function is regulated remains to be explored. In this study, we report for the first time that REGγ can be acetylated mostly on its lysine 195 (K195) residue by CREB binding protein (CBP), which can be reversed by Sirtuin 1 (SIRT1) in mammalian cells. Site directed mutagenesis abrogated acetylation at K195 and significantly attenuated the capability of REGγ to degrade its target substrates, p21 and Hepatitis C virus (HCV) core protein. Mechanistically, acetylation at K195 is important for the interactions between REGγ monomers, and ultimately influences REGγ heptamerization. Biological analysis of cells containing REGγ-WT or REGγ-K195R mutant indicates an impact of acetylation on REGγ-mediated regulation of cell proliferation and cell cycle progression. These findings reveal a previously unknown mechanism in the regulation of REGγ assembly and activity, suggesting a potential venue for the intervention of the ubiquitin-indepdent REGγ-proteasome activity.
  Journal of Biological Chemistry 04/2013; · 4.77 Impact Factor
• Article: Regulation of REGγ cellular distribution and function by SUMO modification.

  Yan Wu, Lu Wang, Ping Zhou, Guangqiang Wang, Yu Zeng, Ying Wang, Jian Liu, Bianhong Zhang, Shuang Liu, Honglin Luo, Xiaotao Li
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  ABSTRACT: Discovery of emerging REGγ-regulated proteins has accentuated the REGγ-proteasome as an important pathway in multiple biological processes, including cell growth, cell cycle regulation, and apoptosis. However, little is known about the regulation of the REGγ-proteasome pathway. Here we demonstrate that REGγ can be SUMOylated in vitro and in vivo by SUMO-1, SUMO-2, and SUMO-3. The SUMO-E3 protein inhibitor of activated STAT (PIAS)1 physically associates with REGγ and promotes SUMOylation of REGγ. SUMOylation of REGγ was found to occur at multiple sites, including K6, K14, and K12. Mutation analysis indicated that these SUMO sites simultaneously contributed to the SUMOylation status of REGγ in cells. Posttranslational modification of REGγ by SUMO conjugation was revealed to mediate cytosolic translocation of REGγ and to cause increased stability of this proteasome activator. SUMOylation-deficient REGγ displayed attenuated ability to degrade p21(Waf//Cip1) due to reduced affinity of the REGγ SUMOylation-defective mutant for p21. Taken together, we report a previously unrecognized mechanism regulating the activity of the proteasome activator REGγ. This regulatory mechanism may enable REGγ to function as a more potent factor in protein degradation with a broader substrate spectrum.
  Cell Research 03/2011; 21(5):807-16. · 8.19 Impact Factor
• Article: REGgamma modulates p53 activity by regulating its cellular localization.

  Jian Liu, Guowu Yu, Yanyan Zhao, Dengpan Zhao, Ying Wang, Lu Wang, Jiang Liu, Lei Li, Yu Zeng, Yongyan Dang, Chuangui Wang, Guang Gao, Weiwen Long, David M Lonard, Shanlou Qiao, Ming-Jer Tsai, Bianhong Zhang, Honglin Luo, Xiaotao Li
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  ABSTRACT: The proteasome activator REGγ mediates a shortcut for the destruction of intact mammalian proteins. The biological roles of REGγ and the underlying mechanisms are not fully understood. Here we provide evidence that REGγ regulates cellular distribution of p53 by facilitating its multiple monoubiquitylation and subsequent nuclear export and degradation. We also show that inhibition of p53 tetramerization by REGγ might further enhance cytoplasmic relocation of p53 and reduce active p53 in the nucleus. Furthermore, multiple monoubiquitylation of p53 enhances its physical interaction with HDM2 and probably facilitates subsequent polyubiquitylation of p53, suggesting that monoubiquitylation can act as a signal for p53 degradation. Depletion of REGγ sensitizes cells to stress-induced apoptosis, validating its crucial role in the control of apoptosis, probably through regulation of p53 function. Using a mouse xenograft model, we show that REGγ knockdown results in a significant reduction of tumor growth, suggesting an important role for REGγ in tumor development. Our study therefore demonstrates that REGγ-mediated inactivation of p53 is one of the mechanisms involved in cancer progression.
  Journal of Cell Science 12/2010; 123(Pt 23):4076-84. · 6.11 Impact Factor